Sembragiline (N-[(3S)-1-[4-[(3-fluorophenyl)methoxy]phenyl]-5-oxo-pyrrolidin-3-yl]acetamide has previously been described in the art. WO 2004/0268251, WO 2006/0971972 and WO 2006/0972703 relate to methods for preparing enantiomerically pure 4-pyrrolidinophenylbenzyl ether derivatives. Sembragiline is a Monoamine oxidase-B type (MAO-B) inhibitor.
Alzheimer's Disease is a brain disease that slowly destroys memory and thinking skills, up to loss of the ability to carry out the simplest tasks. It is the most common cause of dementia among older people. Mild Alzheimer's Disease manifests itself in memory loss and small changes in other cognitive abilities, e.g. getting lost, trouble handling money and managing daily tasks, having some mood and personality changes, etc. In the stage of Moderate Alzheimer's Disease, the control of language, reasoning, sensory processing, and conscious thought are impacted. Memory loss and confusion grow worse, e.g. patients have problems recognizing family and friends and become unable to learn new things, etc. hallucinations, delusions, and paranoia may occur. Severe Alzheimer's Disease is the final stage. Patients cannot communicate anymore and are completely dependent.
MAO-B is involved in Alzheimer's Disease etiology. MAO-B activity is increased in several regions of the brain from an early stage and this is maintained throughout the course of the disease. MAO-B activity is believed to be involved in the production of toxic reactive oxygen species, which are thought to contribute to the pathogenesis of Alzheimer's Disease.
Object of the present invention is to provide stable tablet formulations of different strengths suitable for oral administration of Sembragiline and methods to prepare the same. These formulations have a better manufacturability and performance as previously described formulations.